tbuckley/cabot-search huggingface dataset:
Response by Tabák et al to Letters Regarding Article, “Risk of Macrovascular and Microvascular Disease in Diabetes Diagnosed Using Oral Glucose Tolerance Test With and Without Confirmation by Hemoglobin A1c: The Whitehall II Cohort Study”
Authors: Adam G. Tabák, Naveed Sattar, Mika Kivimäki
Journal: Circulation (2023)

We thank Schmidt and colleagues for their thoughtful comments on our article. 1In agreement with other studies, 2 our data from the Whitehall study show a similarly higher risk of cardiovascular disease associated with incident diabetes at baseline on the basis of a single measurement of hemoglobin A1c (HbA1c; relative risk, 1.66 [95% CI, 1.09-2.52])and oral glucose tolerance test (OGTT, 1.41 [95% CI, 1.04-1.90]).Thus, we agree with the commentators that there is no inherent rank order between different glycemic measures in predicting cardiovascular risk.
High quality Barrett’s endoscopy: inspection time is a critical component
Authors: Madhav Desai, Prateek Sharma
Journal: Endoscopy (2023)

Early neoplasia in patients with Barrett’s esophagus (BE) is often missed during upper endoscopy. Studies have shown that missed cancers could account for up to 25 % of all adenocarcinomas associated with BE [1]. Esophageal adenocarcinoma carries with it a poor survival rate and limited treatment options when found at an advanced stage. Therefore, conducting a high quality upper endoscopy during BE screening and surveillance is necessary for improvement of patient outcomes. Several metrics have been proposed as quality indicators for a high quality BE endoscopy, including measuring the neoplasia detection rate (NDR) [2] and the BE inspection time (BIT).
Safety of guselkumab in patients with psoriasis with a history of malignancy: 5-year results from the VOYAGE 1 and VOYAGE 2 trials
Authors: Andrew Blauvelt, Diamant Thaçi, Kim A Papp, Vincent Ho, Kamran Ghoreschi, Byung Soo Kim, Megan Miller, Yaung-Kaung Shen, Yin You, Daphne Chan, Jenny Yu, Ya-Wen Yang, Mark G Lebwohl, Alice B Gottlieb, Jeffrey Crowley, Peter Foley
Journal: British Journal of Dermatology (2023)

The VOYAGE 1 and 2 studies of guselkumab in moderate-to-severe psoriasis are among the first studies of biologics to include patients with a history of malignancy. In these studies, 18 guselkumab-treated patients had a history of malignancy (excluding nonmelanoma skin cancer) &amp;gt; 5 years prior to enrolment. These 18 patients were exposed to guselkumab for up to 5 years; during this time, one patient had a recurrence of bronchial carcinoma, and three patients developed new malignancies (breast cancer, melanoma and sebaceous carcinoma). All patients with new or recurrent malignancies had underlying risk factors for malignancy. Overall, the results of this analysis in a small population of patients with a history of malignancy support the favourable long-term safety profile of guselkumab.
Prevalence of Diastolic Dysfunction in Adult Survivors of Childhood Cancer
Authors: Cassady Palmer, Wojciech Mazur, Vien T. Truong, Sherif F. Nagueh, James A. Fowler, Kyla Shelton, Vijaya M. Joshi, Kirsten K. Ness, Deo Kumar Srivastava, Leslie L. Robison, Melissa M. Hudson, Isaac B. Rhea, John L. Jefferies, Gregory T. Armstrong
Journal: JACC CardioOncology (2023)

The prevalence of diastolic dysfunction has not been systematically evaluated in a large population of survivors of childhood cancer using established guidelines and standards.This study sought to assess the prevalence and progression of diastolic dysfunction in adult survivors of childhood cancer exposed to cardiotoxic therapy.Comprehensive, longitudinal echocardiographic examinations of adult survivors of childhood cancer ≥18 years of age and ≥10 years from diagnosis in SJLIFE (St. Jude Lifetime Cohort Study) were performed. Diastolic dysfunction was defined based on 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines.Among 3,342 survivors, the median (25th-75th percentiles [quartile (Q)1-Q3]) age at diagnosis was 8.1 years (Q1-Q3: 3.6-13.7 years), 30.1 years (Q1-Q3: 24.4-37.0 years) at the baseline echocardiography evaluation (Echo 1), and 36.6 years (Q1-Q3: 30.8-43.6 years) at the last follow-up echocardiography evaluation (1,435 survivors) (Echo 2). The proportion of diastolic dysfunction was 15.2% (95% CI: 14.0%-16.4%) at Echo 1 and 15.7% (95% CI: 13.9%-17.7%) at Echo 2, largely attributable to concurrent systolic dysfunction. Less than 5% of survivors with preserved ejection fraction had diastolic dysfunction (2.2% at Echo 1, 3.7% at Echo 2). Using global longitudinal strain assessment in adult survivors with preserved ejection fraction (defined with a cutpoint worse than -15.9%), the proportion of diastolic dysfunction increased to 9.2% at baseline and 9.0% at follow-up.The prevalence of isolated diastolic dysfunction is low among adults who received cardiotoxic therapies for childhood cancer. The inclusion of left ventricular global longitudinal strain significantly increased the identification of diastolic dysfunction.
Remote Ischemic Conditioning in Pediatric Cancer Patients Receiving Anthracycline Chemotherapy
Authors: Yiu-fai Cheung, Vivian Wing-yi Li, Edwina Kam-fung So, Frankie Wai-tsoi Cheng, Jeffery Ping-wa Yau, Sau-ying Chiu, Wilfred Hing-sang Wong, Daniel Ka-leung Cheuk
Journal: JACC CardioOncology (2023)

Anthracycline cardiotoxicity is a concern in survivors of childhood cancers. Recent evidence suggests that remote ischemic conditioning (RIC) may offer myocardial protection.This randomized sham-controlled single-blind study tested the hypothesis that RIC may reduce myocardial injury in pediatric cancer patients receiving anthracycline chemotherapy.We performed a phase 2 sham-controlled single-blind randomized controlled trial to determine the impact of RIC on myocardial injury in pediatric cancer patients receiving anthracycline-based chemotherapy. Patients were randomized to receive RIC (3 cycles of 5-minute inflation of a blood pressure cuff placed over 1 limb to 15 mm Hg above systolic pressure) or sham intervention. The intervention was applied within 60 minutes before initiation of the first dose and before up to 4 cycles of anthracycline therapy. The primary outcome was the plasma high-sensitivity cardiac troponin T (hs-cTnT) level. The secondary outcome measures included echocardiographic indexes of left ventricular systolic and diastolic function and the occurrence of cardiovascular events.A total of 68 children 10.9 ± 3.9 years of age were randomized to receive RIC (n = 34) or sham (n = 34) intervention. Plasma levels of hs-cTnT showed a progressive increase across time points in the RIC (P < 0.001) and sham (P < 0.001) groups. At each of the time points, there were no significant differences in hs-cTnT levels or LV tissue Doppler and strain parameters between the 2 groups (all P > 0.05). None of the patients developed heart failure or cardiac arrhythmias.RIC did not exhibit cardioprotective effects in childhood cancer patients receiving anthracycline-based chemotherapy. (Remote Ischaemic Preconditioning in Childhood Cancer [RIPC]; NCT03166813).
Aureane-type sesquiterpene tetraketides as a novel class of immunomodulators with interleukin-17A inhibitory activity
Authors: Xin Tang, Chuanxi Wang, Lei Wang, Feifei Ren, Runqiao Kuang, Zhenhua Li, Xue Han, Yiming Chen, Guodong Chen, Xiuqing Wu, Jie Liu, Hengwen Yang, Xingzhong Liu, Chen Wang, Hao Gao, Zhinan Yin
Journal: Acta Pharmaceutica Sinica B (2023)

Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I (1, 4-11), and two known ones (2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.
Physical Activity During Breast Cancer Therapy Associates With Preserved Exercise Capacity and Cardiac Function (WF97415)
Authors: Moriah P. Bellissimo, Justin M. Canada, Jennifer H. Jordan, Amy C. Ladd, Kerryn W. Reding, Tonya L. Moore, William O. Ntim, Emily M. Heiston, Peter Brubaker, Shannon L. Mihalko, Ralph D’Agostino, Nate O’Connell, Bonnie Ky, Lynne I. Wagner, Mary Helen Hackney, Kathryn E. Weaver, Glenn J. Lesser, Nancy E. Avis, Arnethea L. Sutton, Alexander R. Lucas, R. Lee Franco, Bernard F. Fuemmeler, Fadi N. Salloum, W. Gregory Hundley
Journal: JACC CardioOncology (2023)

Cancer treatment increases cardiovascular disease risk, but physical activity (PA) may prevent cardiovascular disease.
Poziotinib in Treatment-Naive NSCLC Harboring HER2 Exon 20 Mutations: ZENITH20-4, A Multicenter, Multicohort, Open-Label, Phase 2 Trial (Cohort 4)
Authors: Robin Cornelissen, Arsela Prelaj, Sophie Sun, Christina Baik, Mirjana Wollner, Eric B. Haura, Hirva Mamdani, Jonathan W. Riess, Federico Cappuzzo, Marina C. Garassino, John V. Heymach, Mark A. Socinski, Szu-Yun Leu, Gajanan Bhat, Francois Lebel, Xiuning Le
Journal: Journal of Thoracic Oncology (2023)
Supervised Exercise Training for Chronic Heart Failure With Preserved Ejection Fraction: A Scientific Statement From the American Heart Association and American College of Cardiology
Authors: Vandana Sachdev, Kavita Sharma, Steven J. Keteyian, Charina F. Alcain, Patrice Desvigne-Nickens, Jerome L. Fleg, Viorel G. Florea, Barry A. Franklin, Maya Guglin, Martin Halle, Eric S. Leifer, Gurusher Panjrath, Emily A. Tinsley, Renee P. Wong, Dalane W. Kitzman
Journal: Journal of the American College of Cardiology (2023)
Use of digital measurement of medication adherence and lung function to guide the management of uncontrolled asthma (INCA Sun): a multicentre, single-blinded, randomised clinical trial
Authors: Elaine Mac Hale, Garrett Greene, Christopher Mulvey, Matshediso C Mokoka, Job F M van Boven, Breda Cushen, Imran Sulaiman, Vincent Brennan, Lorna Lombard, Joanne Walsh, Sinead Plunkett, Thomas A McCartan, Patrick J Kerr, Richard B Reilly, Cian Hughes, Brian D Kent, David J Jackson, Marcus Butler, Ian Counihan, James Hayes, John Faul, Martin Kelly, Rory Convery, Alexandra M Nanzer, J Mark Fitzgerald, Desmond M Murphy, Liam G Heaney, Richard W Costello, Lorna Lombard, Joanne Walsh, Sinead Plunkett, Thomas A McCartan
Journal: The Lancet Respiratory Medicine (2023)
Australian inflammatory bowel disease consensus statements for preconception, pregnancy and breast feeding
Authors: Robyn Laube, Christian P Selinger, Cynthia H Seow, Britt Christensen, Emma Flanagan, Debra Kennedy, Reme Mountifield, Sean Seeho, Antonia Shand, Astrid-Jane Williams, Rupert W Leong
Journal: Gut (2023)

Objective Because pregnancy outcomes tend to be worse in women with inflammatory bowel disease (IBD) than in those without, we aimed to update consensus statements that guide the clinical management of pregnancy in patients with IBD. Design A multidisciplinary working group was established to formulate these consensus statements. A modified RAND/UCLA appropriateness method was used, consisting of a literature review, online voting, discussion meeting and a second round of voting. The overall agreement among the delegates and appropriateness of the statement are reported. Results Agreement was reached for 38/39 statements which provide guidance on management of pregnancy in patients with IBD. Most medications can and should be continued throughout pregnancy, except for methotrexate, allopurinol and new small molecules, such as tofacitinib. Due to limited data, no conclusion was reached on the use of tioguanine during pregnancy. Achieving and maintaining IBD remission before conception and throughout pregnancy is crucial to optimise maternofetal outcomes. This requires a multidisciplinary approach to engage patients, allay anxieties and maximise adherence tomedication. Intestinal ultrasound can be used for disease monitoring during pregnancy, and flexible sigmoidoscopy or MRI where clinically necessary. Conclusion These consensus statements provide up-to-date, comprehensive recommendations for the management of pregnancy in patients with IBD. This will enable a high standard of care for patients with IBD across all clinical settings.
Gut microbe-derived milnacipran enhances tolerance to gut ischemia/reperfusion injury
Authors: Fan Deng, Jing-Juan Hu, Ze-Bin Lin, Qi-Shun Sun, Yue Min, Bing-Cheng Zhao, Zhi-Bin Huang, Wen-Juan Zhang, Wen-Kao Huang, Wei -Feng Liu, Cai Li, Ke-Xuan Liu
Journal: Cell Reports Medicine (2023)

There are significant differences in the susceptibility of populations to intestinal ischemia/reperfusion (I/R), but the underlying mechanisms remain elusive. Here, we show that mice exhibit significant differences in susceptibility to I/R-induced enterogenic sepsis. Notably, the milnacipran (MC) content in the enterogenic-sepsis-tolerant mice is significantly higher. We also reveal that the pre-operative fecal MC content in cardiopulmonary bypass patients, including those with intestinal I/R injury, is associated with susceptibility to post-operative gastrointestinal injury. We reveal that MC attenuates mouse I/R injury in wild-type mice but not in intestinal epithelial aryl hydrocarbon receptor (AHR) gene conditional knockout mice (AHRflox/flox) or IL-22 gene deletion mice (IL-22−/−). Collectively, our results suggest that gut microbiota affects susceptibility to I/R-induced enterogenic sepsis and that gut microbiota-derived MC plays a pivotal role in tolerance to intestinal I/R in an AHR/ILC3/IL-22 signaling-dependent manner, revealing the pathological mechanism, potential prevention and treatment drugs, and treatment strategies for intestinal I/R.
Unlocking a new dimension in the speed–accuracy trade-off
Authors: Konstantinos Tsetsos
Journal: Trends in Cognitive Sciences (2023)

Why do we sometimes spend too much time on seemingly impossible-to-solve tasks instead of just moving on? Masís et al. provide a new perspective on the speed-accuracy trade-off (SAT), showing that, although prolonging deliberation looks suboptimal in the short run, it is a long-term investment that helps organisms reach proficient performance more rapidly.
Sexual behavior shapes male genitourinary microbiome composition
Authors: Evelyn Toh, Yue Xing, Xiang Gao, Stephen J. Jordan, Teresa A. Batteiger, Byron E. Batteiger, Barbara Van Der Pol, Christina A. Muzny, Netsanet Gebregziabher, James A. Williams, Lora J. Fortenberry, J. Dennis Fortenberry, Qunfeng Dong, David E. Nelson
Journal: Cell Reports Medicine (2023)

The origin, composition, and significance of the distal male urethral microbiome are unclear, but vaginal microbiome dysbiosis is linked to new sex partners and several urogynecological syndromes. We characterized 110 urethral specimens from men without urethral symptoms, infections, or inflammation using shotgun metagenomics. Most urethral specimens contain characteristic lactic acid bacteria and Corynebacterium spp. In contrast, several bacteria associated with vaginal dysbiosis were present only in specimens from men who reported vaginal intercourse. Sexual behavior, but not other evaluated behavioral, demographic, or clinical variables, strongly associated with inter-specimen variance in urethral microbiome composition. Thus, the male urethra supports a simple core microbiome that is established independent of sexual exposures but can be re-shaped by vaginal sex. Overall, the results suggest that urogenital microbiology and sexual behavior are inexorably intertwined, and show that the male urethra harbors female urogenital pathobionts.
Immunoglobulin G-dependent inhibition of inflammatory bone remodeling requires pattern recognition receptor Dectin-1
Authors: Michaela Seeling, Matthias Pöhnl, Sibel Kara, Nathalie Horstmann, Carolina Riemer, Miriam Wöhner, Chunguang Liang, Christin Brückner, Patrick Eiring, Anja Werner, Markus Biburger, Leon Altmann, Martin Schneider, Lukas Amon, Christian H.K. Lehmann, Sooyeon Lee, Meik Kunz, Diana Dudziak, Georg Schett, Tobias Bäuerle, Anja Lux, Jan Tuckermann, Timo Vögtle, Bernhardt Nieswandt, Markus Sauer, Rainer A. Böckmann, Falk Nimmerjahn
Journal: Immunity (2023)

Immunoglobulin G (IgG) antibodies are major drivers of inflammation during infectious and autoimmune diseases. In pooled serum IgG (IVIg), however, antibodies have a potent immunomodulatory and anti-inflammatory activity, but how this is mediated is unclear. We studied IgG-dependent initiation of resolution of inflammation in cytokine- and autoantibody-driven models of rheumatoid arthritis and found IVIg sialylation inhibited joint inflammation, whereas inhibition of osteoclastogenesis was sialic acid independent. Instead, IVIg-dependent inhibition of osteoclastogenesis was abrogated in mice lacking receptors Dectin-1 or FcγRIIb. Atomistic molecular dynamics simulations and super-resolution microscopy revealed that Dectin-1 promoted FcγRIIb membrane conformations that allowed productive IgG binding and enhanced interactions with mouse and human IgG subclasses. IVIg reprogrammed monocytes via FcγRIIb-dependent signaling that required Dectin-1. Our data identify a pathogen-independent function of Dectin-1 as a co-inhibitory checkpoint for IgG-dependent inhibition of mouse and human osteoclastogenesis. These findings may have implications for therapeutic targeting of autoantibody and cytokine-driven inflammation.
Aging microenvironment and antitumor immunity for geriatric oncology: the landscape and future implications
Authors: Binghao Zhao, Bo Wu, Nan Feng, Xiang Zhang, Xin Zhang, Yiping Wei, Wenxiong Zhang
Journal: Journal of Hematology & Oncology (2023)

The tumor microenvironment (TME) has been extensively investigated; however, it is complex and remains unclear, especially in elderly patients. Senescence is a cellular response to a variety of stress signals, which is characterized by stable arrest of the cell cycle and major changes in cell morphology and physiology. To the best of our knowledge, senescence leads to consistent arrest of tumor cells and remodeling of the tumor-immune microenvironment (TIME) by activating a set of pleiotropic cytokines, chemokines, growth factors, and proteinases, which constitute the senescence-associated secretory phenotype (SASP). On the one hand, the SASP promotes antitumor immunity, which enhances treatment efficacy; on the other hand, the SASP increases immunosuppressive cell infiltration, including myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), M2 macrophages, and N2 neutrophils, contributing to TIME suppression. Therefore, a deeper understanding of the regulation of the SASP and components contributing to robust antitumor immunity in elderly individuals with different cancer types and the available therapies is necessary to control tumor cell senescence and provide greater clinical benefits to patients. In this review, we summarize the key biological functions mediated by cytokines and intercellular interactions and significant components of the TME landscape, which influence the immunotherapy response in geriatric oncology. Furthermore, we summarize recent advances in clinical practices targeting TME components and discuss potential senescent TME targets.
T helper 2 cells control monocyte to tissue-resident macrophage differentiation during nematode infection of the pleural cavity
Authors: Conor M. Finlay, James E. Parkinson, Lili Zhang, Brian H.K. Chan, Jesuthas Ajendra, Alistair Chenery, Anya Morrison, Irem Kaymak, Emma L. Houlder, Syed Murtuza Baker, Ben R. Dickie, Louis Boon, Joanne E. Konkel, Matthew R. Hepworth, Andrew S. MacDonald, Gwendalyn J. Randolph, Dominik Rückerl, Judith E. Allen
Journal: Immunity (2023)

The recent revolution in tissue-resident macrophage biology has resulted largely from murine studies performed in C57BL/6 mice. Here, using both C57BL/6 and BALB/c mice, we analyze immune cells in the pleural cavity. Unlike C57BL/6 mice, naive tissue-resident large-cavity macrophages (LCMs) of BALB/c mice failed to fully implement the tissue-residency program. Following infection with a pleural-dwelling nematode, these pre-existing differences were accentuated with LCM expansion occurring in C57BL/6, but not in BALB/c mice. While infection drove monocyte recruitment in both strains, only in C57BL/6 mice were monocytes able to efficiently integrate into the resident pool. Monocyte-to-macrophage conversion required both T cells and interleukin-4 receptor alpha (IL-4Rα) signaling. The transition to tissue residency altered macrophage function, and GATA6
Epigenetic dosage identifies two major and functionally distinct β cell subtypes
Authors: Erez Dror, Luca Fagnocchi, Vanessa Wegert, Stefanos Apostle, Brooke Grimaldi, Tim Gruber, Ilaria Panzeri, Steffen Heyne, Kira Daniela Höffler, Victor Kreiner, Reagan Ching, Tess Tsai-Hsiu Lu, Ayush Semwal, Ben Johnson, Parijat Senapati, Adelheid Lempradl, Dustin Schones, Axel Imhof, Hui Shen, John Andrew Pospisilik
Journal: Cell Metabolism (2023)

The mechanisms that specify and stabilize cell subtypes remain poorly understood. Here, we identify two major subtypes of pancreatic β cells based on histone mark heterogeneity (β
Neuronal identity defines α-synuclein and tau toxicity
Authors: Roman Praschberger, Sabine Kuenen, Nils Schoovaerts, Natalie Kaempf, Jeevanjot Singh, Jasper Janssens, Jef Swerts, Eliana Nachman, Carles Calatayud, Stein Aerts, Suresh Poovathingal, Patrik Verstreken
Journal: Neuron (2023)

Pathogenic α-synuclein and tau are critical drivers of neurodegeneration, and their mutations cause neuronal loss in patients. Whether the underlying preferential neuronal vulnerability is a cell-type-intrinsic property or a consequence of increased expression levels remains elusive. Here, we explore cell-type-specific α-synuclein and tau expression in human brain datasets and use deep phenotyping as well as brain-wide single-cell RNA sequencing of >200 live neuron types in fruit flies to determine which cellular environments react most to α-synuclein or tau toxicity. We detect phenotypic and transcriptomic evidence of differential neuronal vulnerability independent of α-synuclein or tau expression levels. Comparing vulnerable with resilient neurons in Drosophila enabled us to predict numerous human neuron subtypes with increased intrinsic susceptibility to pathogenic α-synuclein or tau. By uncovering synapse- and Ca2+ homeostasis-related genes as tau toxicity modifiers, our work paves the way to leverage neuronal identity to uncover modifiers of neurodegeneration-associated toxic proteins.